The Genomics/Genotyping Core will be responsible for providing high-throughput gene expression data, including validation of expression of select candidate genes, as well as genotyping and sequencing services, to include DNA and RNA isolation, quantification, plating and tracking, to achieve the overall aims of this SCCOR application entitled, "Molecular Determinants of Pulmonary Arterial Hypertension." This Core will support the procurement and analysis of tissue samples from patients with scleroderma and idiopathic pulmonary arterial hypertension (PAH) and various and relevant rat and mouse models for PAH. In genomics studies, patterns of gene expression will be analyzed within each clinical and experimental condition. This approach will allow us to determine both concordantly and discordantly regulated clusters of genes, link these gene clusters with physiological measurements, and identify gene profiles responsible for development and maintenance of well-defined clinical phenotypes. The genetics component will facilitate validation of the physiological importance of genes and "high risk" alleles in well-characterized cohorts to detect novel variants and to test for association with variants in candidate genes. With this technology, we will be able to provide an exploration of novel sentinel genes and regulatory pathways involved in PAH and facilitate the selection of candidate genes for high-throughput genotyping through microarray analysis. The Core will interact directly with: Core A, which will assist with financial management, with Core B for integration of information technology solutions with the clinical database system, and with Core E for downstream proteomic studies of genes identified in the high-throughput studies. These comprehensive studies will complement the rigorous phenotypic characterization provided by the clinical projects and similarly, will provide the foundation for exploration of relevant genes associated with the animal models of PAH in the basic projects. Specific Aims are: 1) to provide an integrated laboratory facility to support gene expression profiling and genotyping of samples from well- characterized patients with PAH, experiment and project management, primer and assay design, and computational/analytical activities associated with genomic and genetic data;and 2) provide an efficient, cost-effective high-throughput expression profiling and genotyping service to meet the demands of diverse individual projects.